In cases of extreme and life threatening conditions such as renal, liver and cardiac failure, physicians have successfully transplanted tissues between genetically distinct individuals. Even when care is taken to reduce the genetic differences between the host and donor, the recipients of these grafts must usually be given drugs that reduce the activity of their immune system so that the graft is not rejected. Such immuno-suppression entails substantial risks. Even when such immuno-suppression is well tolerated, there are considerable difficulties attendant in minimizing the antigenic differences (matching) between the donor and the recipient that increases the costs and reduces the availability of this mode of therapy. Furthermore, not all tissues can be successfully transplanted between genetically distinct persons.
In principle, for example, diabetes mellitus, one of the most common and, in the longterm, one of the most debilitating chronic diseases, could be "cured" by a successful transplant of the tissue that secrete insulin, the islets of Langerhans. Despite the magnitude of the problem, the availability of islets from cadaveric donors and the successful experience in other situations, e.g., renal, cardiac and hepatic transplantation, there is presently no practical protocol that routinely provides for the survival of histoincompatible islet cells.
The probable causes for this absence may be several. In diabetes mellitus, the disease itself makes immuno-suppression especially hazardous, as diabetics are highly susceptible to infection. Also it appears that some immuno-suppressive agents, e.g., cyclosporine, are directly toxic to islets in high doses and can adversely affect graft survival, while others, e.g., glucocorticoids, are known to increase the subject's insulin requirements and may indirectly jeopardize both the survival and the beneficial effects of the graft. Lastly, in many instances diabetes results from autoimmunity directed toward the islets. To the extent such individuals are immunologically "primed" towards non-allelic islet antigens, their graft rejection would be accelerated. Thus, as an alternative to the present methods of promoting graft survival, which reduce the host's immunity, there is a need in the transplantation art for a method to specifically render the graft invisible to the host's immune system or resistant to its effects.